title: Rhes and AGS1/Dexras1 affect signaling by dopamine D1 receptors through adenylyl cyclase.
abstract: The GTP binding proteins Rhes and AGS1/Dexras1 define a subfamily of the Ras superfamily and have been shown to affect signaling by G-protein-coupled receptors. We tested the effects of both proteins at an early stage of signaling by dopamine receptors, activation of adenylyl cyclase. Rhes decreased dopamine D1 receptor agonist-stimulated cAMP accumulation in a pertussis toxin-sensitive manner. It had no effect on cAMP accumulation in the absence of agonist. AGS1/Dexras1, on the other hand, decreased cAMP accumulation in both vehicle-treated and agonist-treated cells, resulting in a higher percentage of stimulation by agonist or a higher signal-to-noise ratio. The effects of AGS1/Dexras1 on cAMP accumulation were not blocked by pertussis toxin, suggesting that it may produce these effects through interaction with a G(α) i monomer. Both Rhes and AGS1/Dexras1 were associated with GTP-bound G(α) i in pull-down assays. However, Rhes had no effect on the ability of activated D2 receptor to inhibit cAMP. Neither Rhes nor AGS1/Dexras1 interacted with the D1 receptor in pull-down assays. These findings show that, in addition to its well-known effects on signaling through Gi-coupled receptors, AGS1/Dexras1 can affect signaling through a Gs/olf-coupled receptor. Furthermore, the results suggest that Rhes exerts some of its effects by interacting with G(α) i.
authors.affiliation: Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana. lhar14@lsuhsc.edu
authors.forename: Laura M
authors.initials: LM
authors.lastname: Harrison
authors.forename: Youe
authors.initials: Y
authors.lastname: He
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D016466:CHO Cells; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D037342:Pertussis Toxin / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection / Q000379:methods; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C494644:3-allyl-6-chloro-7,8-dihydroxy-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D005576:Colforsin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; C498511:Rasd1 protein, mouse; C488189:Rasd2 protein, mouse; D018631:ras Proteins; D000262:Adenylyl Cyclases